Expression In Biopsy Specimens Research Articles

Clinical Features of Newly Diagnosed CD25-Positive Follicular Lymphoma

AbstractAbstract 1543 Background:CD25 (the alpha chain of the IL-2 receptor) has been shown to be expressed in hairy cell leukemia cells and a small subset of normal B cells. Recently, we reported that CD25 is expressed in a subset of diffuse large B-cell lymphoma (DLBCL) (ASH 2011 118:2666). However, its expression in follicular lymphoma (FL) has yet to be fully examined. The aim of this study was to clarify the clinical features of newly diagnosed CD25+ FL. Patients and Methods:Eighty-four patients with newly diagnosed CD25+ FL who were admitted to our hospital between 2002 and 2012 were retrospectively evaluated. Biopsy specimens from lymph nodes or related tissues were analyzed by flow cytometry (FCM) using a combined method of single- and two-color staining. CD25 expression was defined as positivity of >20% of clonal B cells with CD19 or 20 expression >70% in a gated region. Results were compared with patients with reactive lymphadenopathy (n=27), DLBCL at initial presentation (n=91), and FL at relapse (n=13). Results:CD25 expression in untreated patients with FL (mean±SD, 10.6±9.9%; n=84) was almost equivalent to that in patients with reactive lymphadenopathy (mean±SD, 9.1±4.4%; n=27, P =0.3), and lower than that in untreated patients with DLBCL (mean±SD, 28.5±31.1%; n=91, P <0.001). There was a trend of a higher CD25 expression in biopsy specimens from relapsed FL than in those from newly diagnosed FL (mean±SD, 18.6±16.3 vs. 10.6±9.9%, respectively, P=0.077). With the sum of treated and untreated CD25+ FL, two-color FCM showed that the mean±SD of CD25/CD19 and CD25/CD20 dual expression was 28.5±26.5% (n=4) and 28±24.3% (n=4), respectively. The patients with newly diagnosed CD25+ (more than 20%) FL (n=10) showed some clinical features such as B symptoms (P =0.09), soluble IL-2 receptor titers of more than 5,000 U/ml (P =0.013), and advanced ages over 60 (P =0.16), compared with CD25- FL patients (n=74). Besides, there were some differences between CD25+ and CD25- FL in terms of histology grade 3 (50 vs. 32%, respectively, P=0.29) and the presence of t(14;18) (33 vs. 56%, respectively, P=0.27).Patients with FL at the initial presentation underwent rituximab-containing chemotherapy (n=68), radiotherapy (n=4), and observation (n=12). Kaplan–Meier analysis showed poorer progression-free survival (PFS) and overall survival (OS) in patients with CD25+ FL than that in patients with CD25- FL (2-year PFS, 36 vs. 82%, respectively, P <0.001; 6-year OS, 47 vs. 88%, respectively, P <0.01). Multivariate analysis revealed that CD25 expression is a significant prognostic factor for PFS (HR 6.4, 95%CI 2.4–17.4, P <0.001) and OS (HR 6.6, 95%CI 1.2–36.9, P= 0.027), which is independent of FLIPI score variables. Conclusion:Newly diagnosed CD25+ FL may constitute a distinct subgroup associated with aggressive clinical features and an inferior prognosis. CD25 may be a new prognostic marker, and could be a therapeutic target in FL patients. Disclosures:No relevant conflicts of interest to declare.

P-0297 Predictive/Prognostic Value of TS, KI-67, Egfr, MLH-1, MSH-2 and Trg in Locally Advanced Rectal Cancer Treated with Neoadjuvant Chemoradiation (Bmg-B1-Study)

ABSTRACT Introduction Preoperative 5-fluorouracil/capecitabine based chemoradiation (CRT) is standard treatment in locally advanced rectal cancer (LARC) patients (pts). The aim of this Bologna Multidisciplinary Group (BMG-B1) study was to evaluate the predictive and prognostic value of Tumor Regression Grade (TRG) and pathological biomarkers (thymidylate synthetase/TS, epidermal growth factor receptor/EGFR, Ki-67, p53, Bcl-2, MLH1 and MSH2). Methods Between December 2001 to January 2011 we evaluated 149 pts with cT3-T4 N-/+ rectal adenocarcinoma and location ≤12 cm from the anal margin. Preoperative CRT consisted of radiotherapy 50.4 Gy in 28 daily fractions in combination with 5-fluorouracil continuous infusion or capecitabine +/- oxaliplatin. Rectal surgery with total mesorectal excision was performed 6-8 weeks after neoadjuvant treatment. Pathological examination of surgical specimens included the TRG according to Dworak (TRG0=no regression, TRG1=minor regression, TRG2=moderate regression, TRG3=good regression TRG4=complete regression). TS, EGFR, Ki-67, p53, Bcl-2, MLH1 and MSH2 were immunohistochemically determined in pretreatment biopsies and surgical specimens. Serial sections of formalin-fixed, paraffin-embedded tissues were stained with anti-TS (clone TS106/4H4B1, Zymed Lab. Inc., Invitrogen USA), anti-EGFR (clone DAK-H1-WT, DakoCytomation USA), anti-Ki-67 (clone MM1, Novocastra Lab.UK), anti-p53 (clone BP53-12, Novocastra Lab. UK), anti-Bcl-2 (clone 124, DakoCytomation. USA), anti-MLH1 (clone G168-15, Pharmingen, USA), anti-MSH2 (clone FE11, Zymed Lab. Inc., Invitrogen USA) using a biotin free ready-to-use amplification system (Dako Advance HRP, DakoCytomation DK). Results Immunohistochemistry results of 100 biopsies and 97 surgical specimens were available. After a median follow-up of 60.3 months (2-122) we observed 4.7% local recurrences, 12.7% distant recurrences, and 13.4% deaths. TRG grade 1, 2, 3, and 4 were observed respectively in 22.6%, 35.4%, 25.5%, 16.5% of patients. Patients with TRG grade 0-1 compared to patients with TRG grade 2-4 had significant worse disease free survival (DFS) (p=0.008) and overall survival (p=0.04). High TS expression in biopsy specimens is related with TRG grade 0-1 (p=0.009). High EGFR expression in surgical specimen is related with low DFS (p=0.01). The high decrease in Ki-67 expressions between biopsy and surgical specimen is related with TRG grade 3-4 (p=0.001). The others evaluated biomarkers did not showed clinical correlations. Conclusion In BMG-B1 Study TRG grade and EGFR expression in operative specimen after CRT showed a prognostic value. High TS expression in biopsy before CRT was related to worse pathological response, and high Ki-67 decrease after CRT is related to best response.

Variations at HER2 and hormone receptor status in primary and metastatic sites of breast cancer patients.

e11023 Background: Evaluation of hormone receptors (ER/PR) and Her2-Neu is important for hormonal and anti-Her2 treatments. The parameters are generally estimated in primary tumors and it is unclear whether re-evaluation of metastatic lesions will be effective during follow-up. Methods: The primary aim of this study was the compare Her2 and HR (ER/PR) status in primary and metastatic tissues of breast cancer patients. HR and Her2 expression in biopsy specimens obtained from primary tumor and their metastatic lesions of 44 breast cancer patients, followed-up during 1995-2010 at Baskent University Hospital were analyzed. Results: Of 44 patients 29.5% were found Her2 (+), 54,5 % ER (+) and 45.4% PR (+) in primary site. Metastatic regions excised or biopsied as following: Bone 31.8% (14/44), liver 27.3% (12/44), skin 25% (11/44), lung 9.1% (4/44), brain 4.5% (2%44), bone marrow 4.5 (2/44), ovaries 4.5% (2/44), stomach, abdominal LAP and pelvic mass 2.3% (3/44). Positification rate of ER status in metastatic sites was detected as 4.5% (2/44), when positive in primary tumors, negatification rate was detected as 20.5%. The positification rate of PR status in metastatic sites, while being negative in primary tissue was 13.6% (6/44); and negativication rate in metastatic lesions, being positive in primary tumor was 27.3% (12/44). The positivication rate of Her2 expression in metastatic lesions while being negative in primary tissue was 4.5% (2/44); and negativication rate while being positive in primary tumor was detected as 13.6% (6/44). When the hormone receptor status and Her2 expression of the patients followed-up are evaluated, receptor variation was detected in 23 of 44 patients. Conclusions: Our study confirms that biological properties of breast cancer may vary among primary tumors and asynchronised metastatic lesions. Further prospective studies are needed to better define the discordance of Her2 or HR status at primary tissue and metastatic sites.

Mo1286 Tumor Diameter and KI-67 Expression in Biopsy Specimens as Diagnostic Markers for Discriminating Between Adenoma and Early-Stage Cancer in Patients With Ampullary Tumors

Mo1286 Tumor Diameter and KI-67 Expression in Biopsy Specimens as Diagnostic Markers for Discriminating Between Adenoma and Early-Stage Cancer in Patients With Ampullary Tumors

Assessment of thymidylate synthase expression in biopsy specimens and corresponding resection specimens of non‐small‐cell lung cancer

Pemetrexed (Pem) is a potent inhibitor of thymidylate synthase (TS), and has shown efficacy in the treatment of non-small-cell lung cancer (NSCLC). TS expression in NSCLC biopsy specimens may correlate with the tumour responses to TS-inhibiting agents. As TS is not homogeneously expressed, our aim was to test whether TS expression in biopsy specimens may be representative for the whole tumour and can be used for therapeutic assessment. We immunohistochemically analysed TS expression in biopsy and corresponding resection specimens of 100 consecutive NSCLCs. The samples were subgrouped according to TS expression levels, and the degree of agreement between the biopsy and the corresponding resection specimen was calculated. TS expression-based grouping according to one cut-off criterion (high or low expression) led to concordant results between biopsy and resection specimens. When more than one cut-off criterion was used, the results were significantly different. Thymidylate synthase expression levels in NSCLC biopsy specimens may correspond to TS expression of the whole tumour when robust scoring systems are applied. Further studies are needed to determine whether high or low TS expression in NSCLC biopsy specimens is of predictive value, and whether it may allow the selection of patients who will benefit from Pem treatment.

Increased CD133 expression after preoperative chemoradiotherapy in rectal cancers other than mucin-rich tumors

This study is to characterize the sequential change in CD133 expression after preoperative chemoradiotherapy (CRT) in rectal cancer and its impact on postoperative prognosis. Forty-one patients with rectal cancer who had received CRT before surgery were selected retrospectively. In each case, immunohistochemical analysis was performed to compare CD133 expression in biopsy specimens taken before and after CRT. After CRT, CD133 expression was significantly increased in 14 (34%) patients, mildly increased in 25 (61%), and decreased in 2 (5%). However, no mucin-rich tumors showed high CD133 expression before or after CRT (p < 0.001). Disease-free survival and overall survival were significantly poorer in patients with significantly increased CD133 (p = 0.049 and p = 0.038, respectively). Increased CD133 after CRT is a significant prognostic factor in rectal cancer patients treated with preoperative CRT and surgical resection. CD133 might be an essential cancer stem cell marker.

Expression of mast cell–associated genes is upregulated in adult eosinophilic esophagitis and responds to steroid or dietary therapy

Expression of mast cell–associated genes is upregulated in adult eosinophilic esophagitis and responds to steroid or dietary therapy

Expression of Cytokeratin 7 as a Histological Marker of Cholestasis and Stages of Primary Biliary Cirrhosis

The aim of this study was to estimate cytokeratin 7 (CK-7) expression in biopsy specimens of patients with different stages of primary biliary cirrhosis and clinicopathological patterns (cholestatic and hepatitic) and its correlation with some biochemical and pathological parameters and to examine a diagnostic value of CK-7 expression. A total of 82 biopsy specimens of patients with primary biliary cirrhosis were analyzed. CK-7 expression was graded by 4 grades depending on the extent into parenchymal areas and bile duct epithelium. The correlations of CK-7 expression grade with copper deposition, bile duct/portal tract ratio, bilirubin concentration, and activity of alkaline phosphatase and gamma-glutamyl transpeptidase were studied. CK-7 expression was evaluated as a marker of cholestasis (cholestatic pattern) and inflammation (hepatitic pattern). A positive correlation of CK-7 expression grade with copper-binding protein grade (r=0.698, P<0.0001; OR=6.199, P<0.0001), serum bilirubin level (r=0.375, P=0.001), and alkaline phosphatase activity (r=0.276, p=0.014) was found. CK-7 expression grades correlated positively with histological stages of primary biliary cirrhosis (r=0.639, P<0.000) and negatively with granulomas (r=-0.432, P<0.0001; OR=0.173, P=0.0011). CK-7 expression is a sensitive marker of bile duct injury, which correlated well with histological stages of primary biliary cirrhosis, copper deposits, and biochemical markers of cholestasis: serum bilirubin level and alkaline phosphatase activity. Evaluation of CK-7 expression may improve the diagnosis of this serious and progressive disease. It is recommended to evaluate copper staining together with cytokeratin 7 expression in liver biopsy specimens for more precise diagnostic evaluation of asymptomatic primary biliary cirrhosis.

Inflammatory Bowel Disease-Associated Interleukin-33 Is Preferentially Expressed in Ulceration-Associated Myofibroblasts

Interleukin-33 (IL-33) is a novel member of the interleukin-1 family that induces mucosal pathology in vivo and may drive fibrosis development and angiogenesis. To address its potential role in inflammatory bowel disease, we explored its tissue expression in biopsy specimens from untreated ulcerative colitis patients, observing a 2.6-fold up-regulation of IL-33 mRNA levels, compared to controls. Immunohistochemical analyses of surgical specimens showed that a prominent source of IL-33 in ulcerative colitis lesions were ulceration-associated myofibroblasts that co-expressed the fibroblast marker heat shock protein 47, platelet-derived growth factor receptor (PDGFR)β, and, in part, the myofibroblast marker α-smooth muscle actin (SMA). In contrast, IL-33-positive myofibroblasts were almost absent near the deep fissures seen in Crohn's disease. A screen of known and putative activators of IL-33 in cultured fibroblasts revealed that the Toll-like receptor-3 agonist poly (I:C) was among the strongest inducers of IL-33 and that it synergized with transforming growth factor-β, a combination also known to boost myofibroblast differentiation. Experimental wound healing in rat skin revealed that the de novo induction of IL-33 in pericytes and the possible activation of scattered, tissue-resident IL-33(+)PDGFRβ(+)αSMA(-) fibroblast-like cells were early events that preceded the later appearance of IL-33(+)PDGFRβ(+)αSMA(+) cells. In conclusion, our data point to a novel role for IL-33 in mucosal healing and wound repair and to an interesting difference between ulcerative colitis and Crohn's disease.

Vascular Endothelial Growth Factor-C Associated with Computed Tomography Used in the Diagnosis of Lymph Node Metastasis of Bladder Carcinoma

Vascular endothelial growth factor C (VEGF-C) has been demonstrated to stimulate the growth of lymphatic vascular endothelium. The purpose of this study is to determine whether VEGF-C associated with computed tomography (CT) has a relationship with lymph node metastasis in bladder transitional cell carcinoma (BTCC). One hundred twenty seven cases of BTCC were studied: first, both plain and enhanced CT scans of abdomen and pelvis were performed preoperatively; second, VEGF-C protein expressions in tumor cells were tested by immunohistochemistry postoperatively; and finally, detailed pathological findings for lymph node metastasis were recorded. VEGF-C expressions in tumor bladder cells were significantly higher than those in normal bladder epithelium. In the group of BTCC-positive, VEGF-C was significantly correlated with lymph node metastasis (p <0.01). Sensitivity, specificity and accuracy of VEGF-C in the diagnosis of lymph node metastasis of bladder carcinoma were 87.0, 67.9, and 74.8%, respectively. Sensitivity, specificity and accuracy of CT were 47.8, 80.2, and 68.5%, respectively. When VEGF-C visually correlated with CT scan in the detection of lymph node metastasis, sensitivity was 91.3%; specificity was 84.0% and accuracy was 86.6%. Positive VEGF-C was significantly correlated with lymph node metastasis of bladder carcinoma. VEGF-C expression in biopsy specimens may be beneficial in predicting pelvic lymph nodes. It can improve accuracy when combined with CT.

Analysis of differential gene expression in colorectal cancer and stroma using fluorescence-activated cell sorting purification

Tumour stroma gene expression in biopsy specimens may obscure the expression of tumour parenchyma, hampering the predictive power of microarrays. We aimed to assess the utility of fluorescence-activated cell sorting (FACS) for generating cell populations for gene expression analysis and to compare the gene expression of FACS-purified tumour parenchyma to that of whole tumour biopsies. Single cell suspensions were generated from colorectal tumour biopsies and tumour parenchyma was separated using FACS. Fluorescence-activated cell sorting allowed reliable estimation and purification of cell populations, generating parenchymal purity above 90%. RNA from FACS-purified and corresponding whole tumour biopsies was hybridised to Affymetrix oligonucleotide microarrays. Whole tumour and parenchymal samples demonstrated differential gene expression, with 289 genes significantly overexpressed in the whole tumour, many of which were consistent with stromal gene expression (e.g., COL6A3, COL1A2, POSTN, TIMP2). Genes characteristic of colorectal carcinoma were overexpressed in the FACS-purified cells (e.g., HOX2D and RHOB). We found FACS to be a robust method for generating samples for gene expression analysis, allowing simultaneous assessment of parenchymal and stromal compartments. Gross stromal contamination may affect the interpretation of cancer gene expression microarray experiments, with implications for hypotheses generation and the stability of expression signatures used for predicting clinical outcomes.

Expression of breast cancer resistance protein is associated with a poor clinical outcome in patients with small-cell lung cancer

ATP-binding cassette (ABC) transporter and DNA excision repair proteins play a pivotal role in the mechanisms of drug resistance. The aim of this study was to investigate the expression of ABC transporter and DNA excision repair proteins, and to elucidate the clinical significance of their expression in biopsy specimens from patients with small-cell lung cancer (SCLC). We investigated expression of the ABC transporter proteins, P-glycoprotein (Pgp), multidrug resistance associated-protein 1 (MRP1), MRP2, MRP3, and breast cancer resistance protein (BCRP), and the DNA excision repair proteins, excision repair cross-complementation group 1 (ERCC1) protein and breast cancer susceptibility gene 1 (BRCA1) protein, in tumor biopsy specimens obtained before chemotherapy from 130 SCLC patients who later received platinum-based combination chemotherapy, and investigated the relationship between their expression and both response and survival. No significant associations were found between expression of Pgp, MRP1, MRP2, MRP3, ERCC1, or BRCA1 and either response or survival. However, there was a significant association between BCRP expression and both response (p=0.026) and progression-free survival (PFS; p=0.0103). BCRP expression was significantly predictive of both response and progression-free survival (PFS) in SCLC patients receiving chemotherapy. These findings suggest that BCRP may play a crucial role in drug resistance mechanisms, and that it may serve as an ideal molecular target for the treatment of SCLC.

Immunohistochemical expression of BCRP and ERCC1 in biopsy specimen predicts survival in advanced non-small-cell lung cancer treated with cisplatin-based chemotherapy

Purpose The aim of this study was to determine the prognostic value of expression of ATP binding cassette (ABC) transporter proteins and DNA repair gene proteins by immunohistochemically staining tumor biopsy specimens from patients with advanced non-small-cell lung cancer (NSCLC) being treated with platinum-based chemotherapy. Experimental design Expression of ABC transporter proteins, including BCRP (breast cancer resistance protein) and MRP2 (multidrug resistance proteins 2), and the DNA-repair-related proteins, ERCC1 (excision repair cross-complementation group 1) and BRCA1 (breast cancer type 1 susceptibility protein) was assessed immunohistochemically in 156 tumor samples from untreated stage IV NSCLC patients. All of the patients had received platinum-based chemotherapy. Response to chemotherapy, progression-free survival (PFS), and overall survival were compared in relation to expression of each of the proteins and to clinicopathological factors. Results High ERCC1 expression was associated with short survival (237 days vs. 453 days, log-rank P = 0.03), but not with response to chemotherapy or PFS. And high BCRP expression was associated with short survival (214 days vs. 412 days, log-rank P = 0.02) but not with response to chemotherapy or PFS. Multivariate analysis confirmed that negativity for the expression of BCRP tends to be an independent variable related to overall survival ( P = 0.06). Conclusions This study examined ERCC1 and BCRP expression in biopsy specimens as candidates for predictors of the survival of patients with advanced NSCLC treated with platinum-based chemotherapy.

XIAP expression and its predictive significance of prognosis in stage IIB osteosarcomas

Objective To evaluate X-linked inhibitor of apoptosis protein (XIAP) expression in biopsy specimens from the patients with stage IIB osteosarcomas before chemotherapy to study XIAP expression and its predictive significance of prognosis in stage IIB osteosarcomas.

Clinical significance of tissue levels of matrix metalloproteinases and tissue inhibitors of metalloproteinases in gastric cancer

Matrix metalloproteinases (MMPs) are one of the major classes of proteolytic enzymes involved in tumor invasion and metastasis, being inhibited by naturally occurring tissue inhibitors of metalloproteinases (TIMPs). In this study, we examined the expression of MMP-2, MMP-9, membrane-type 1 (MT1)-MMP, TIMP-1, and TIMP-2 in biopsy tissues of gastric cancer, and the correlation between their expression and clinicopathological parameters. Biopsy specimens from 66 patients with gastric carcinoma were available for this study. To determine the expression of MMP-2, MMP-9, MT1-MMP, TIMP-1, and TIMP-2, semiquantitative reverse transcriptase-polymerase chain reaction (RT-PCR) was carried out on tumor and normal tissues, respectively, sampled during diagnostic gastroscopic examination. Immunohistochemical staining of representative samples using monoclonal antibody directed against MT1-MMP was done, and the clinicopathological variables were reviewed retrospectively. The expression level of MMPs and TIMPs was evaluated using the tumor : normal (T/N) ratios of MMPs and TIMPs. The T/N ratio of MT1-MMP mRNA showed a significant correlation with lymph node metastasis and tumor stage (P < 0.05). The other RT-PCR data of MMP-2, MMP-9, TIMP-1, and TIMP-2 did not show any significant correlation with clinicopathological parameters. Immunohistochemistry for MT1-MMP showed a positive immunoreaction in gastric adenocarcinoma and negative staining in normal mucosa. The correlation between the increased expression of MT1-MMP and clinicopathological variables reflects a role in predicting the aggressive behavior of gastric cancer. Because an RT-PCR assay can be performed on biopsy specimens obtained before surgery, an evaluation of MT1-MMP expression in biopsy specimens by RT-PCR may provide useful preoperative information on tumor aggressiveness.

Vascular endothelial growth factor‐C expression in bladder transitional cell cancer and its relationship to lymph node metastasis

To elucidate the role of vascular endothelial growth factor-C (VEGF-C) in bladder transitional cell carcinoma (TCC), examining VEGF-C expression in bladder TCC tissue and the association of VEGF-C with clinicopathological features, as the expression of VEGF-C in several carcinomas is significantly associated with angiogenesis, lymphangiogenesis and regional lymph node metastasis, but there are few reports of VEGF-C expression in bladder TCC. The study included 45 patients with bladder TCC; VEGF-C expression was assessed by immunohistochemistry and the association between VEGF-C expression and angiogenesis, as evaluated by microvessel density (MVD), was examined. There was VEGF-C expression in the cytoplasm of tumour cells, but very little in the normal transitional epithelium. VEGF-C expression was significantly associated with tumour size, pathological T stage, pathological grade, lymphatic-venous involvement and pelvic lymph node metastasis (all P < 0.05). Multivariate analysis showed that VEGF-C expression was an exclusive independent factor influencing pelvic lymph node metastasis. Moreover, the patients with high VEGF-C expression had a markedly poorer prognosis than those with no or low VEGF-C expression (P = 0.014). A multivariate analysis based on the Cox proportional hazard model showed that lymph node metastasis was only an independent prognostic factor in the multivariate analysis using the Cox regression model (P = 0.010). The present study provides evidence supporting the involvement of VEGF-C expression in the promotion of lymph node metastasis in bladder TCC. Examination of VEGF-C expression in biopsy specimens might be beneficial in predicting pelvic lymph node metastasis.

Erythropoietin receptor expression in biopsy specimens from patients with uterine cervix squamous cell carcinoma

Hypoxia, an important mechanism of radioresistance, is a strong stimulus for erythropoietin (EPO) production. The stimulatory effects of EPO are mediated through the activation of its receptors, EPO receptors (EPORs). The objective of this study is to determine whether EPORs are expressed in biopsy specimens of patients with squamous cell carcinoma of the cervix. Eighteen biopsy specimens were studied after obtaining Institutional Review Board-approved consent. Standard immunohistochemistry techniques were utilized. Expression of EPORs was present in 16 out of 18 (88.9%) specimens. The intensity (qualitative) and the frequency (semiquantitative) of EPORs expression showed a statistically significant correlation (P= 0.00379). Statistical analysis was performed to determine whether EPORs expression is related to other parameters such as age, FIGO stage, histologic grade, and hemoglobin levels. Only age showed a statistically significant correlation with EPORs frequency of expression (P= 0.00878). Currently, work is in progress in our laboratory to study the radiobiologic effects of EPO on the radiation response of cultured cancer cell lines in vitro.

Erythropoietin receptor expression in biopsy specimens from patients with uterine cervix squamous cell carcinoma

Erythropoietin receptor expression in biopsy specimens from patients with uterine cervix squamous cell carcinoma

Down‐Regulation of Human Leukocyte Antigen Class I and II and β2‐Microglobulin Expression in Human Herpesvirus‐7–Infected Cells

Human herpesvirus (HHV)-7 is a ubiquitous virus that infects >90% of adults. We show that HHV-7 impairs beta2-microglobulin and human leukocyte antigen (HLA) class I and II expression in lymphoid cells in vitro. Accordingly, infected cells were more sensitive to peripheral blood natural cytotoxic activity than were uninfected cells. Analysis of beta2-microglobulin and HLA expression in biopsy specimens from human submandibular glands confirmed the ability of HHV-7 to modulate the expression of these antigens in vivo. We demonstrate that the down-modulation of HLA by HHV-7 is linked to viral replication and is not merely a consequence of the interaction of virions with the cell surface. Infected cells can therefore efficiently escape host immune pressure, which might explain the persistence of HHV-7-positive cells in several kinds of tumors and chronic infectious diseases.

Predictive value of COX-2 for the effect of chemoradiotherapy on esophageal squamous cell carcinoma

Cyclooxygenase-2 (COX-2) displays anti-apoptotic functions related to angiogenesis or blocking of bcl-2 functions. COX-2 overexpression has been found in various human malignancies, including esophageal squamous cell carcinoma (ESCC). The present study examined correlations between expression of COX-2 mRNA and ESCC responses to chemoradiotherapy (CRT). Expression of COX-2 mRNA obtained from 29 biopsy specimens before CRT was quantified using reverse transcriptase-polymerase chain reaction (RT-PCR) using Sybr Green I on the Roche LightCycler system. CRT comprised 5-fluorouracil plus cisplatin and 40 Gy of radiation. Mean COX-2 mRNA score was significantly higher in tumors (1222) than in normal epithelium (50; p=0.05). Expression of COX-2 mRNA was high in 14 patients, low in 8 and absent in 7. The effective response to CRT was achieved in 18 patients. Mean COX-2 mRNA score was significantly higher in ineffective cases (2910) than in effective cases (190; p<0.05). CRT was more effective in patients with low COX-2 mRNA expression than in those with high expression. COX-2 mRNA expression in biopsy specimens was closely related to CRT effectiveness. Examination of COX-2 mRNA expression is useful for predicting the effect of CRT in patients with ESCC.